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Biomedical subjects

A Cook

Publications and source records attributed to A Cook.

At least 19 recordsLinked to original sources

Explaining differences in English hospital death rates using routinely collected data.

OBJECTIVES: To ascertain hospital inpatient mortality in England and to determine which factors best explain variation in standardised hospital death ratios. DESIGN: Weighted linear regression analysis of routinely collected data over four years, with hospital standardised mortality ratios as the dependent variable. SETTING: England. SUBJECTS: Eight million discharges from NHS hospitals when the primary diagnosis was one of the diagnoses accounting for 80% of inpatient deaths. MAIN OUTCOME MEASURES: Hospital standardised mortality ratios and predictors of variations in these ratios. RESULTS: The four year crude death rates varied across hospitals from 3.4% to 13.6% (average for England 8.5%), and standardised hospital mortality ratios ranged from 53 to 137 (average for England 100). The percentage of cases that were emergency admissions (60% of total hospital admissions) was the best predictor of this variation in mortality, with the ratio of hospital doctors to beds and general practitioners to head of population the next best predictors. When analyses were restricted to emergency admissions (which covered 93% of all patient deaths analysed) number of doctors per bed was the best predictor. CONCLUSION: Analysis of hospital episode statistics reveals wide variation in standardised hospital mortality ratios in England. The percentage of total admissions classified as emergencies is the most powerful predictor of variation in mortality. The ratios of doctors to head of population served, both in hospital and in general practice, seem to be critical determinants of standardised hospital death rates; the higher these ratios, the lower the death rates in both cases.

Data Collection

Morphologic spectrum of Ebstein's malformation: revisitation relative to surgical repair.

OBJECTIVE: Our aim was to elucidate the morphologic spectrum of Ebstein's malformation of the tricuspid valve with regard to diagnosis and the feasibility of surgical repair, in the light of the currently favored reconstructive techniques. METHODS: We examined 23 autopsied hearts. Taking the displacement of the septal and mural leaflets of the abnormal tricuspid valve as our diagnostic criterion, we focused subsequently on the location of the distorted valvular orifice and the attachment and formation of the anterosuperior leaflet. We also assessed the dimensions of the components of the right ventricle relative to the plane of the displaced valvular orifice. RESULTS: In all hearts, the septal and mural leaflets were hinged at various points within the inlet of the right ventricle. In many cases, however, these leaflets were virtually absent. The plane of the effective tricuspid valvular orifice was displaced anterosuperiorly to varying degrees. In the most severe forms, the valvular mechanism took the form of a 1-leaflet valve. The length of the functional right ventricle when compared with the left ventricle ranged proportionally from 0.6 to 1. 1 (mean, 0.9). CONCLUSIONS: Ebstein's malformation is much more than simple "downward displacement" of the leaflets. In essence, the valvular orifice is formed within the ventricular cavity at the junction of the atrialized inlet and functional ventricular components. When surgical intervention becomes necessary, it is essential to make a detailed assessment of both valvular and ventricular abnormalities.

Adolescent

Allergen exposure, atopy and smoking as determinants of allergy to rats in a cohort of laboratory employees.

This study aimed to examine the relationship between exposure to rat urinary allergens, atopic status, smoking and the development of allergic symptoms and specific sensitization. It is a case-referent analysis of a cohort of 342 newly employed laboratory animal workers. Cases comprised persons developing symptoms of laboratory animal allergy or a positive skin prick test to rat urinary allergens; each was matched with up to two asymptomatic referents. Subjects were assigned to categories of exposure based on measurements of airborne rat urinary allergens. Of the cases, 80% reported that their symptoms started within 2 yrs of employment. The odds ratio (OR) for development of each symptom type (respiratory, eye or nose and skin) and of an immediate skin test reaction was increased in those with direct contact with rats. A gradient of increasing OR for the development of any such symptom across exposure categories was found; for respiratory symptoms and skin test reactions the OR for subjects in the highest exposure category were lower than those in intermediate categories, a pattern attenuated when the analysis was confined to outcomes developing within 2 yrs of first exposure. Atopy increased the OR of most outcomes as did cigarette smoking, although there was no evidence of a relationship between smoking and the development of a specific skin test reaction. In conclusion, allergen exposure was confirmed as the most important determinant of laboratory animal allergy; by implication, measures to reduce exposure may be the most effective means to reduce its incidence.

Adult

Outflow uropathy: occupational disorder?

This paper alerts physicians, health care workers, and employers to a probable connection between voluntary, infrequent voiding and urinary dysfunction. The dysfunction includes abnormal uroflow patterns, increased urethral resistance, abnormal post-void residuals, chronic trigonitis, and urethrovesical inflammatory polyps. A review of intermittent uroflow and obstructive uroflow patterns reveals that all females in this study worked long hours without voiding.

Adult

The experiences of one divisional group of GPs in introducing computers into clinical practice.

OBJECTIVES: To explore the experiences of GPs who have introduced computers into their practices, particularly for clinical use. METHODS: GPs who have introduced computers into their practice for clinical use were identified by a telephone survey of the membership of the Monash Division, Melbourne, Victoria. Eleven 'clinical users' participated in semi-structured interviews to elucidate their experiences of installing computers in their consulting rooms, including their beliefs on how this process could have been given more support. RESULTS: Sixty-two of 67 practices participated in the initial telephone survey. Sixteen percent of responding practices were using computers for clinical purposes, with 11% issuing computerised prescriptions. Interviews with clinical users revealed that most had learned about computer hardware and software through their own independent enquiries. However, the GPs believed that divisions have an increasing role in providing training, education, and offering independent advice about the purchase of appropriate computer systems. DISCUSSION: This group of GPs adopted computers for clinical purposes without much assistance from the medical profession. Their experience of the process of computerisation illustrated that lack of training posed problems as did lack of support. Half of the sample felt that divisions may be able to provide training and education, independent advice and act as a forum to discuss and develop ideas, and thus ease some of the problems associated with adopting new technologies. CONCLUSION: Several suggestions are made for GPs and divisions to assist in the process of computerisation.

Australia

Genetic linkage analysis of collagen-induced arthritis in the mouse.

The genetic susceptibility to collagen-induced arthritis (CIA) in mice, the most commonly used model for rheumatoid arthritis, has been analyzed. The highly susceptible B10.RIII strain was crossed with the resistant RIIIS/J strain and the F2 intercross mice were subjected to genomic screening using microsatellite markers. These strains share the MHC region on chromosome 17, known to be of importance in CIA (this locus is named Mcia1). The same cross has earlier been used to map the major genes outside the MHC controlling chronic relapsing experimental allergic encephalomyelitis (EAE). It was found that the major locus controlling CIA (Mcia2; lod 4.12) was located on chromosome 3 in the same region as one of the major loci controlling EAE (Eae3). The linkage was reproduced in a mouse strain in which the locus was isolated on the B10.RIII background at the N4I2 generation. A second putative locus was identified on chromosome 13 (lod 3.13). The present finding identifies new loci outside the MHC controlling CIA and provides evidence that mouse CIA is controlled by polymorphic genes.

Animals

Dietary sources of nutrients among US adults, 1989 to 1991.

OBJECTIVE: To identify major food sources of 27 nutrients and dietary constituents for US adults. DESIGN: Single 24-hour dietary recalls were used to assess intakes. From 3,970 individual foods reported, 112 groups were created on the basis of similarities in nutrient content or use. Food mixtures were disaggregated using the US Department of Agriculture (USDA) food grouping system. SUBJECTS/SETTING: A nationally representative sample of adults aged 19 years or older (n = 10,638) from USDA's 1989-91 Continuing Survey of Food Intakes by Individuals. ANALYSES PERFORMED: For each of 27 dietary components, the contribution of each food group to intake was obtained by summing the amount provided by the food group for all respondents and dividing by total intake from all food groups for all respondents. RESULTS: This article updates previous work and is, to the authors' knowledge the first to provide such data for carotenes, vitamin B-12, magnesium, and copper. Beef, yeast bread, poultry, cheese, and milk were among the top 10 sources of energy, fat, and protein. The following other major sources also contributed more than 2% to energy intakes: carbohydrate: yeast bread, soft drinks/soda, cakes/cookies/ quick breads/doughnuts, sugars/syrups/jams, potatoes (white), ready-to-eat cereal, and pasta; protein: pasta; and fat: margarine, salad dressings/mayonnaise, and cakes/ cookies/quick breads/doughnuts. Ready-to-eat cereals, primarily because of fortification, were among the top 10 food sources for 18 of 27 nutrients. APPLICATIONS/CONCLUSIONS: These analyses are the most current regarding food sources of nutrients and, because of disaggregation of mixtures, provide a truer picture of contributions of each food group.

Adult

The effect of cimetidine on the pharmacokinetics of epirubicin in patients with advanced breast cancer: preliminary evidence of a potentially common drug interaction.

Epirubicin is known to be metabolized in the liver. Therefore, drugs such as cimetidine, which inhibit the cytochrome P-450 enzyme system or reduce liver blood flow, may reduce the plasma clearance of epirubicin. In a small study, epirubicin 100 mg/m2 every 3 weeks was administered intravenously to eight patients, who also received oral cimetidine (400 mg b.d. for 7 days starting 5 days before chemotherapy) with either the first or second cycles. Epirubicin pharmacokinetics and liver blood flow (idocyanine green clearance) were assessed at each course. The areas under the plasma concentration time curves (AUCs) were used to compare the systemic exposure to epirubicin and its metabolites with each course. The estimated median percentage increase (95% confidence interval CI) in the AUC with cimetidine were: epirubicin 50% (95% CI -18 to 193, epirubicinol 41% (95% CI 1 to 92). Despite the small numbers studied, the increase in the active metabolite epirubicinol was significant (P < 0.05). These changes in exposure were not explained by reduced cytochrome P-450 activity as the 7-deoxy-doxorubicinol aglycone AUC was not reduced (357% increase: 95% CI 17 to 719) or by a decrease in liver blood flow (17% increase: 95% CI -39 to 104). Cimetidine is likely to be coprescribed or self-administered with epirubicin and therefore clinicians should be aware of this potential interaction.

Administration, Oral

Depressive symptom differences in hospitalized, medically ill, depressed psychiatric inpatients and nonmedical controls.

This study compared depressive and anxious symptoms in chronic medically ill individuals and depressed psychiatric inpatients using conceptually based standardized measures of cognitions and symptoms. Seventy-five hospitalized medical patients, 52 depressed psychiatric inpatients, and 25 normal controls were assessed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987), the Mood and Anxiety Symptom Questionnaire, Hamilton Rating Scales of Anxiety and Depression, Hospital Anxiety and Depression Scales, Beck Depression Inventory, Cognitions Checklist, and Hopelessness Scale. Analysis revealed that depression in medical patients was best distinguished by symptoms of anhedonia, low positive affect, and physiological hyperarousal, whereas syndromal depression in psychiatric inpatients was specifically characterized by negative cognition symptoms. Implications are discussed for assessing depression in medically ill populations.

Adolescent

Serological and cellular immune responses to non-structural proteins in animals infected with FMDV.

In order to provide a rational base for the evaluation of FMDV non structural proteins as diagnostic probes, we have performed systematic longitudinal studies of the humoral and cellular immune responses to these proteins in animals infected with different FMDV serotypes. Although primary antibody responses to all the non structural proteins were observed, antibody titres were highly variable, ranging from insignificant in some cases, to clearly positive in others. In general, even the obvious positive responses were of short duration. For this reasons, discrimination between infected and vaccinated cattle is only possible at a herd level, and in our experiments the most useful target was the non structural protein 3A, although addition of 2C and 3C would provide a more sensitive test. As an alternative, with the major advantage of use directly on living cattle in the field, recombinant non structural proteins were evaluated in Delayed Type Hypersensitivity (DTH) skin tests. With this test, which measures Th1 type cellular immune responses, the most T cell immunogenic non structural proteins were 2B, 2C and 3D. Thus, DTH skin test could be a very useful tool to differentiate infected from vaccinated cattle.

Animals

Dietary sources of nutrients among US children, 1989-1991.

OBJECTIVE: To identify major food sources of nutrients and dietary constituents for US children. METHODS: Twenty-four-hour dietary recalls were collected from a nationally representative sample of children age 2 to 18 years (n = 4008) from the US Department of Agriculture's 1989-1991 Continuing Survey of Food Intakes by Individuals. For each of 16 dietary constituents, the contribution of each of 113 food groups was obtained by summing the amount provided by the food group for all individuals and dividing by total intake from all food groups for all individuals. RESULTS: Milk, yeast bread, cakes/cookies/quick breads/donuts, beef, and cheese are among the top 10 sources of energy, fat, and protein. Many of the top 10 sources of carbohydrate (yeast bread, soft drinks/sodas, milk, ready-to-eat cereal, cakes/cookies/quick breads/donuts, sugars/syrups/jams, fruit drinks, pasta, white potatoes); protein (poultry, ready-to-eat cereal, pasta); and fat (potato chips/corn chips/popcorn) also contributed >2% each to energy intakes. Ready-to-eat cereal is among the top contributors to folate, vitamin A, vitamin C, iron, and zinc intakes. Fruit drinks, containing little juice, contribute approximately 14% of total vitamin C intakes. CONCLUSIONS: Fortified foods are influential contributors to many vitamins and minerals. Low nutrient-dense foods are major contributors to energy, fats, and carbohydrate. This compromises intakes of more nutritious foods and may impede compliance with current dietary guidance.

Adolescent

The fragile X syndrome.

Fragile X syndrome (FXS) is the most common cause known of inherited developmental disability. New and widely available techniques in DNA analysis allow both affected individuals and carriers to be tested from a simple blood sample. It is now recognised that a wide range of clinical severity occurs in both sexes. Specific treatment and interventional strategies are now available and of great benefit to individuals, families and carers. Genetic counselling allows families to make informed decisions. General practitioners can play a central role in detection and management of this syndrome.

Fragile X Syndrome

CBP/p300 as a co-factor for the Microphthalmia transcription factor.

The Microphthalmia basic-Helix-Loop-Helix-Leucine Zipper (bHLH-LZ) transcription factor (Mi) plays a crucial role in the genesis of melanocytes; mice deficient for a functional (Microphthalmia) gene product lack all pigment cells. We show here that the Mi activation domain resides N-terminal to the DNA-binding domain and that as little as 18 amino acids are sufficient to mediate transcription activation. The minimal activation region of Mi is highly conserved in the related transcription factor TFE3 and is predicted to adopt an amphipathic alpha-helical conformation. This region of Mi is also highly conserved with a region of E1A known to be essential for binding the CBP/p300 transcription cofactor. Consistent with these observations, the Mi activation domain can interact in vitro with CBP specifically through a region of CBP required for complex formation with E1A, P/CAF and c-Fos, and anti p300 antibodies can co-immunoprecipitate Mi from both melanocyte and melanoma cell lines. In addition, co-transfection of a vector expressing CBP2 (aas 1621-1891) fused to the VP16 activation domain potentiated the ability of Mi to activate transcription, confirming the significance of the CBP-Mi interaction observed in vitro. These data suggest that transcription activation by Mi is achieved at least in part by recruitment of CBP. The parallels between transcription regulation by Microphthalmia in melanocytes and MyoD in muscle cells are discussed.

Adenovirus E1A Proteins